Brains at risk: The curious link between strokes and Alzheimer’s disease

By Dyani Lewis

World authority on strokes and post-stroke care Prof Vladimir Hachinski discusses how strokes can amplify the effects of Alzheimer’s disease and vice versa, and how lifestyle factors can be protective against both.

Hi. I’m Dyani Lewis. Thanks for joining us. As we head into old age, our chances of suffering from a range of serious, life-altering conditions increases. Among the most concerning are those that affect our brain -- Conditions like stroke and Alzheimer’s disease that can erode the very essence of who we are. On the surface, these two conditions seem very different. Alzheimer’s disease creeps up on people over many years, whereas strokes can occur very suddenly, seemingly coming out of nowhere to cause what can be irreparable damage, if they aren’t treated quickly. I’m joined on Up Close today by a world-renowned neurologist who has been investigating an intriguing link between these two quite different neurological conditions. Professor Vladimir Hachinski has been a pioneer in stroke care and prevention for many years. He is Professor of Neurology and Epidemiology at the University of Western Ontario in Canada and he is visiting Melbourne as the Allan and Maria Myers International Fellow at The Florey Institute of Neuroscience and Mental Health. Welcome to Up Close, Vladimir.

VLADIMIR HACHINSKI
Thank you.

DYANI LEWIS
Vladimir, you’ve spent a great deal of your career investigating strokes, what you term brain attacks. Could you start by explaining what a stroke is? What’s happening in the brain of someone who is having a stroke?

VLADIMIR HACHINSKI
Well, a stroke is the sudden loss of a function of the brain due to the closure of a blood vessel or the bursting of a blood vessel. Typically, the type of signs that you see are the inability to speak, the inability to move a side of the body, the inability to feel in one side of the body and also visual symptoms -- inability to see in one eye or half or both eyes. That’s what a stroke is. What is happening is that if you have a closure of blood vessel, the brain is very sensitive to the lack of oxygen and glucose, which is what it lives on. It takes only a few minutes before the brain begins to lose function and then if the blood is not restored, to actually die. So a stroke is really the dying of a part, if the blood flow is cut off. The other type is if you have a bleeding into the brain, which is actually physical damage to that part of the brain, where the bleeding occurs.

DYANI LEWIS
The damage that occurs during a stroke can be in very precise locations within the brain. Yet, there are ways of having generalised symptoms and signs of a stroke and, in fact, you came up with the Hachinski Ischaemic Score, which is a checklist of general symptoms that can identify a stroke. How is that possible, given the different locations where a stroke can occur?

VLADIMIR HACHINSKI
Well, fortunately, we know a lot about the brain anatomy and depending what the symptoms and signs are, we can tell fairly reliably what part of the brain is involved simply by interrogating the patient, interrogating a witness and examining the patients. Now, with imaging, of course, we can very precise, because you can see exactly where the damage is.

DYANI LEWIS
What about cognitive changes that occur? Are there cognitive deficits that people have when they have a stroke?

VLADIMIR HACHINSKI
Yes. About 20 per cent of people who have a stroke will end up with dementia. In other words, enough cognitive impairment that that will interfere will self-sufficiency. At first, it was thought it was simply brain damage, enough damage to the brain from strokes. But it turns out that some patients who only have a stroke in one part of the brain begin to behave as if they had Alzheimer’s disease. Our researcher is centred on the fact that a stroke can precipitate Alzheimer’s disease. It has been shown pathologically that the changes of Alzheimer’s disease actually occur in normal people as well. It’s a question of quantity and timing. If somebody has changes of Alzheimer’s disease, they may not have any consequences in their cognitive ability. But if they also have little strokes, then this doubles the chance that they will have dementia. So what we believe is that in people who already have some changes of Alzheimer’s disease, then have a stroke, this tips them over into having Alzheimer’s disease. In experiments, we have shown the interaction and the good news is that we can supress some of these interactions by using anti-inflammatory agent experimentally.

DYANI LEWIS
In terms of Alzheimer’s disease, often when we think of the kinds of decline that occur with Alzheimer’s, we’re thinking about memory loss and that sort of thing. Is that the same kind of cognitive decline that occurs in someone who has simply had a stroke?

VLADIMIR HACHINSKI
No. Well, first of all, both stroke and Alzheimer’s disease take a long to happen. In Alzheimer’s disease, it takes about 20 years before the first molecular mischief and the first clinical manifestation. There’s a long latency. For stroke, we’re discovering it’s similar. In other words, for each stroke that we know about, there are six we do not know about. They are small strokes called silent strokes. Except that that is not a good term, because if you examine these patients they often will have some cognitive impairment. Instead of having episodic memory disorder, which is what is the hallmark of Alzheimer’s disease, the hallmark of vascular disease is executive function -- the ability to plan, to multitask, to problem solve.

DYANI LEWIS
So with the silent strokes that you’re talking about, obviously, there’s no way of a patient being able to, I guess, undertake any rehabilitation post silent stroke, because they wouldn’t know that they’ve had it. But there is rehabilitation that can occur with a stroke that you do know about that isn’t silent, isn’t there?

VLADIMIR HACHINSKI
Yes. I mean, one of the big discoveries in the recent past is that rehabilitation works. In fact, the largest rehabilitation stroke study ever to be performed is led by Julie Bernhardt, here at the University of Melbourne with 52 centres in five countries. So that will give us many answers as to what part works in what groups, at what age, what stroke severity. Of course, this is linked very closely with the studies in what’s called neuroplasticity. The ability of the brain to adapt to injury. Here The Florey Institute has a major role to play.

DYANI LEWIS
In terms of impairment that can occur building up over many years preceding, perhaps, a major stroke, are there any ways of screening people for those early signs?

VLADIMIR HACHINSKI
Yes. There are. In fact, we’re doing a study to see whether testing people early can identify people at higher risk. Of course, the idea would be to begin intervening much earlier. But the awareness of silent vascular disease is something relatively recent and the studies that need to be done have not yet been done. Although, there’s great interest in pursuing them.

DYANI LEWIS
So what kind of test would that be? Do you have to put them in an MRI scanner, for example?

VLADIMIR HACHINSKI
No. Well, I mean, ultimately, that’s what you want to do. But no, the simplest thing is a screening instrument that’s the MoCA, the Montreal Cognitive Assessment Instrument. That gives you an idea whether there’s any impairment. If they pass the screening test, they’re probably okay. If they fail the screening test, depending on what other risk factors they have, you may want to do an MRI or a CAT scan. Then you will be able to see these little silent infarcts.

DYANI LEWIS
So that’s just like a very short problem solving test.

VLADIMIR HACHINSKI
Yes. It’s a very simply test. It has scored on 30 points. So that’s a screening test. So the next step is okay, so they have an impairment. What is the vascular component? Now, many years ago, I invented a little scale, the one you referred to. Now we’ve produced a simpler version, which is simply five questions that do not require an examination. One of the studies we want to perform is to see whether we can do a very simple screening test with the MoCA and then identify a vascular factor and then treat it. Because you want to have something that’s cheap, easily administered. We also have done a study comparing the MoCA test in the pencil and paper version with an iPad version. People prefer that. Even older people. I was surprised by that. So we’re moving into an era where people are taking more responsibility for their health and detecting these sort of problems long before any catastrophic expressions, like a clinical stroke or dementia.

DYANI LEWIS
Presumably, with the knowledge that there has been some decline, you can rehabilitate.

VLADIMIR HACHINSKI
Well, the rehabilitation that we know about has to do with clinical strokes. There has been no time to really perform studies about the mini strokes. However, the fact that they occur relatively commonly probably means that there is a fair amount of recovery and the brain compensates for these small lesions. Because the remarkable thing about stroke is not the damage it inflicts, but the recovery it allows. So I would be optimistic that the silent strokes are also compensated for. To give you an idea how common they are, by the age of 62, one in 10 people have had a silent stroke and that increases with age.

DYANI LEWIS
This is Up Close. I’m Dyani Lewis and in this episode we’re talking about the relationship between Alzheimer’s disease and strokes with neurologist Professor Vladimir Hachinski. Vladimir, Alzheimer’s disease is quite a different condition to stroke, in that the most drastic changes are building up over a long time. It’s very progressive. When did you start to think about a connection between stroke and Alzheimer’s disease.

VLADIMIR HACHINSKI
Well, the first thing that gave me that gave me the curiosity to pursue this is that the scale that I invented was meant to separate Alzheimer’s disease from what I called multi-infarct dementia. In other words, multiple strokes. Then it was found that that scale is very good at identifying pure Alzheimer’s disease. But it does not distinguish between having mixed dementia, in other words, the one that have Alzheimer’s disease and stroke and pure stroke. So then I began thinking, well, that must mean that a lot of the elderly people actually have both pathologies. That is now unquestionable. They do. But the next question was stroke and Alzheimer changes, are they simply fellow travellers or partners in crime? The most convincing evidence came from a nun study in the United States. What happened there is that they had a hundred per cent donation rate of the nuns who died donated their brains. So if they looked at the brains of nuns who had the pathological diagnosis of Alzheimer’s disease, in other words, pathology was looked at it, had all the lesions, said okay, this person must have had Alzheimer’s disease. Only 57 per cent of those nuns had trouble in their life. So it wasn’t just the lesions of Alzheimer’s disease. If then they had a stroke that involved the cortex, the rind of the brain, then 75 per cent of them had dementia. If they had small deep strokes and they had pathological changes of Alzheimer’s disease, then 93 per cent of them had difficulty in life. So based on that, my colleague, David Cechetto, and I developed an animal model. We found that in our animal model, we make the rats Alzheimer-like by inducing deposition of amyloid, Abeta, which is an abnormal protein that is toxic to the brain.

DYANI LEWIS
These are the classic plaques that you see in Alzheimer’s.

VLADIMIR HACHINSKI
These are the classic plaques of Alzheimer’s disease and we found that if we produced a stroke in the presence of amyloid, the stroke was bigger and it grew. Inflammation was greater and instead of settling down, it flared. This had consequences in the rat, because we tested them for the ability to learn and remember. Of course, their memory got worse, their ability to learn went worse. But the good news again, as my colleague, David Cechetto, was able to use anti-inflammatory agents and prevent many of these changes, which gives us the hope that we can do the same in people.

DYANI LEWIS
So the anti-inflammatories, were they making the Alzheimer’s background better or was it the anti-inflammatories that were making the strokes less severe?

VLADIMIR HACHINSKI
Well, I think inflammation is something that contributes to the deterioration. More recently, we’ve had a collaboration with a colleague in Montreal called Alex Thiel. He began looking at people and he found that if somebody has had a stroke and you look at their brains, then their cognitive status and six months correlates with the amount of inflammation of the white matter. So we think that the white matter inflammation contributes to the cognitive deterioration after stroke and since we’ve been able to prevent that in the laboratory, we are now trying to find the best anti-inflammatory agent, so we can begin testing in people.

DYANI LEWIS
Coming back to your statement of whether they’re common travellers in the path to old age or whether they’re actually interacting in some way, I mean, are they just a case of an unhealthy brain in one case is going to be worse at surviving the onslaught of a second problem? Or is there something more fundamental where if you’re at risk of one, then you are automatically at risk of another?

VLADIMIR HACHINSKI
Well, first of all, lesions in the brain don’t add up, they multiply. Each time you add something, there is something of the overall function that is decreased. I think we have evidence of a direct interaction, because we think that the ischemia, the lack of blood, then produces inflammation. Inflammation produces deposition of amyloid. Amyloid produces more inflammation, so you have this malignant triangle, which we can interrupt with drugs. So that’s one of the direct effects. Now, you made the statement as to whether automatically if you have one, you have the other. I think the evidence is that if you have one, you’re more likely to develop the other, but it’s not automatic, because it depends on the amount of Alzheimer’s disease, it depends on the stroke and where it’s located. But there is an interaction and the interaction is treatable.

DYANI LEWIS
In the case of stroke, there are a number of lifestyle factors that can increase your risk of having a stroke. Can you tell us what those are?

VLADIMIR HACHINSKI
Yes. The main one is high blood pressure, unhealthy diet, a diet high in calories and in sugars and in salt and trans fats. Physical inactivity. Those are the main ones. Now, the flip side of that is that hypertension is highly treatable. Physical activity is easy to undertake and, in fact, there is good evidence not only from epidemiological data, but also from laboratory work that exercise does very good things to the brain. It makes the brain function better. It makes a healthier body. It’s a powerful protective. In terms of diet, there have been good studies done now in which they show that the Mediterranean diet, one that is heavy on nuts and vegetables and olive oils and small amounts of meat, that that reduces strokes, dementia and heart disease by about 20 per cent. So we do have the elements to change the odds of developing stroke and Alzheimer’s disease.

DYANI LEWIS
Do these same lifestyle factors that play a role in stroke also play a role in Alzheimer’s?

VLADIMIR HACHINSKI
That answer’s yes. That’s the good news. That if you do those exercises, if you eat well, if you look after yourself, then you’re preventing not only stroke, but if not preventing, delaying Alzheimer’s disease.

DYANI LEWIS
If only lifestyle weren’t so notoriously difficult to change. Is there any way that you can really impress upon people the importance of modifying their behaviour?

VLADIMIR HACHINSKI
Well, the answer is love and not the one you’re thinking. It’s first of all commitment to another human being who cares. In fact, we’re carrying out a study in which we have comparing usual care, which means we see patients who have had a warning of a stroke or a minor stroke and then the usual care is they see a specialist, like ourselves, we send a letter to the family doctor. Or to work with a layperson who becomes their partner. They advise on lifestyle. We found in a pilot study that working with that individual was a very powerful motivator. We found that there was a strong trend towards decreasing blood pressure and decreasing weight. So I think that there is precedent for saying that if you make a commitment to someone else, you’re in a better position to really accomplish what you want. I think we will have the results of the study in two years. In the meantime, we know that working with someone, committing to someone makes a difference.I’ll give you a personal example. Some years ago, I slipped on the ice, which you don’t have here. I ripped out a tendon in my left shoulder and then I had to have it operated on. The operation went well, but then I was assigned a physiotherapist, and he was a small man, and I’m large and he had to work very hard on me. He gave me these bands. A yellow band, an orange band and a red band. I was supposed to do these damn exercises. I thought to myself, I’m not going to be using this for sports, my left shoulder. After all, I’m right handed. Whatever normal movement I have in the left shoulder, I will maintain. But he would work so hard on me and say, ‘Doctor, have you done your exercise?’ I didn’t have the heart to say I didn’t, so I did and I have a perfect shoulder. So this is an example of if you commit to someone else, they encourage you, you’re more likely to have it.So I think that if we show that our study is positive, this will be widely applicable, because I think having someone of the same sex and similar age, who cares about whether you’re controlling risk factors or not can make a great difference. Almost certainly, this is something that we’ll be using in the future, because it is difficult to change your own behaviour, if you haven’t got the encouragement or the commitment to someone else.

DYANI LEWIS
I’m Dyani Lewis and my guest today is neurologist Professor Vladimir Hachinski. We’re talking about strokes and Alzheimer’s disease here on Up Close. Vladimir, the other thing that is often used to prompt people to change their lifestyle is if something has already gone wrong. But is there a way of, I guess, identifying years in advance whether you will be at risk in the future?

VLADIMIR HACHINSKI
Yes. There are scales. There’s a thing called Framingham Stroke Risk Index, that gives you the likelihood you will have a stroke within 10 years. There is also a dementia scale, but there has been no scale to incorporate both. In fact, my daughter and I are working on a book for the public. We’re developing an index. So I’ll give you an idea and say, okay, here are your risk factors. This is the likelihood you’ll develop either stroke or dementia. Then if you change the risk, you’ll change your score. One of the powerful motivators is feedback. To say that if you behave yourself today, then in 20 years, you won’t have a stroke, that’s too remote. But if you look at indexes, oh my goodness, my chance of having a stroke are now 51 per cent, and then you do something about it, and say gosh, it’s only a third now. That makes a difference. That’s feedback.

DYANI LEWIS
What about the role of medications in altering risk factor? You mentioned anti-inflammatories before. Should people be taking anti-inflammatories if they already have Alzheimer’s to prevent strokes?

VLADIMIR HACHINSKI
No. I don’t think we’re ready. I think we’re working in the laboratory. We’re modelling what anti-inflammatory agent at what dose, when. I think in terms of medication, I think follow the doctor’s advice. Certainly, there’s a range of drugs for blood pressure treatment. There are statins for high cholesterol. There are drugs for diabetes and I think the question you haven’t asked me, but I’m sure is on your mind is whether everybody should take aspirin. The answer is no. The reason is this. That aspirin is a very powerful drug that in the long term it decreases by a small margin the likelihood of a stroke in a woman and of heart attack in a man. However, the risk of bleeding is so high that unless the person is at a very high risk of having heart attacks or stroke, they should not be taking it regularly. On medical advice that’s different.

DYANI LEWIS
What about genetic factors? I mean, we all have a different genetic background, and there are well known genes, such as the ApoE gene in Alzheimer’s that increases risk.

VLADIMIR HACHINSKI
Yes.

DYANI LEWIS
So does this gene or other genes increase the risk of both conditions? Or are those risk...

VLADIMIR HACHINSKI
Yes. There are genetic risk factors for both. But most of them have a small impact. There isn’t one gene that determines somebody if going to have Alzheimer’s disease. The most powerful one is ApoE4, as you mentioned. It turns out that having the ApoE4 multiplies the risk of having dementia considerably. For example, if somebody has high blood pressure in mid-life and they also have the ApoE4, it increases the risk about 11 fold, which is enormous. The good however is that if blood pressure is treated, then that risk is not much higher than if they didn’t have the wrong gene. There’s evidence from Finland, the same is true for physical inactivity. In other words, if there’s physical inactivity and the wrong gene, the risk goes up very quickly. However, the very people who at higher risk because of their bad gene also benefit the most. So luckily, most of our fate is still in our hands when it comes to risks.

DYANI LEWIS
Given this relationship between stroke and Alzheimer’s that you’ve been investigating, what does this mean in terms of how we manage these conditions when someone has been diagnosed with one or the other?

VLADIMIR HACHINSKI
Well, at the moment, unfortunately, we’re really concentrating on the end stage. So if someone has Alzheimer’s disease, the best we can do is to give them comfort or drugs to moderate the symptoms. At the moment, we have no treatments. The difficulty is that by the time that they have a full blown dementia, the brain is too destroyed to make a big difference. That’s why the emphasis in making the shift earlier. It’s never too late, but earlier is better.

DYANI LEWIS
Many countries have an aging population. What has this meant for how common stroke and Alzheimer’s are in communities today?

VLADIMIR HACHINSKI
The absolute numbers are increasing, because there are more old people and that’s the single most powerful determinant of the incidents of stroke and dementia. However, there is some good news and that is that in developed countries that the incidence of stroke has been cut in half. Unfortunately, in the developing countries it has doubled, mainly because of the adaptation of Western lifestyles. In dementia, likewise there’s good news. One study from Holland, one study from Sweden that show that the incidence of dementia, in other words, the number of demented people per hundred thousand population is actually decreasing. So we’re doing something right and we can do more.

DYANI LEWIS
What is that something right that’s driving that down?

VLADIMIR HACHINSKI
Yeah. For stroke, I think we’re fairly certain it’s control of risk factors. For dementia, it’s less clear. But these are the very countries where they also have shown a dramatic decrease in the stroke rate. Given what I’ve said before about the relationship, almost certainly the decrease in stroke is also decreasing the dementia or at least delaying it. Because they also have shown that. That the younger cohorts, the younger groups have even less dementia than the older groups. So clearly, we’re doing something right. Again, this is the basis for optimism. It will take concerted effort at all levels; individual, community level, at the policy makers level and at the global level.

DYANI LEWIS
What role do governments and policy makers have in changing the incidence of stroke and Alzheimer’s in our community?

VLADIMIR HACHINSKI
A very important one. First of all, there is no health without brain health. Secondly, that brain health depends on the mothers and the child and their education. Thirdly, our brains are our future, because we’re in a knowledge based society and we need to have better brains to have a better world. So this is very much relevant to whatever we’re doing for the future. Now, the governments have become very interested, in part for the negative side. That is that dementia is a tremendous cost. In Britain, for example, it’s the costliest condition. More expensive than stroke, than heart disease, than cancer and Prime Minister Cameron last year proclaimed dementia as a priority. There are a number of follow up meetings that are going to take place to make sure that that is on the agenda at the G8. So finally, I think, governments are catching on to the fact that if we’re going to prevent these costly disabling conditions, that we must do something now.

DYANI LEWIS
Vladimir Hachinski, thank you for being our guest today on Up Close.

VLADIMIR HACHINSKI
You’re very welcome.

DYANI LEWIS
Professor Vladimir Hachinski is Professor of Neurology and Epidemiology at the University of Western Ontario in Canada.